Today an opinion piece that I wrote about CIRM was published in the San Francisco Chronicle. The unusual element here is that the article is critical of CIRM. More specifically I raised concerns about a recent political trend at CIRM under its new President Randy Mills lobbying for dramatically weaker stem cell regulatory oversight. The Chronicle piecewas first posted online on Thursday on the paper’s website. I encourage you to read it when you get a chance.

For me the tipping point to action was Mills’ recent opinion piece on FoxNews with former Republican Senator Bill Frist that I believe was anti-FDA in tone and utilized hype (e.g. words like “miracles”, “gift”, and “beautiful” medicine) to promote a deregulatory agenda. This extreme plan includes conditional approval of unproven stem cell therapies and elimination of the requirement for Phase III clinical trials in certain cases, which would be very risky to patients and the stem cell field.

Mills also recently gave a speech at a conservative group (the self-styled “Bipartisan” Policy Center or BPC at which Frist is a leader) that counterproductively characterized the FDA as the one big problem for the field. Note that BPC also wants to charge patients to be in clinical trials to get experimental therapies. Historically if anything changed hands in such situations it was patients getting something in return for being so brave to be in clinical trials.

As I pointed out in my opinion piece in the Chronicle, the stem cell status quo is not getting the job done, but this is only in part due to the FDA and the changes that BPC and CIRM are advocating for are too radical. These proposed changes also fit with the REGROW Act, a bill that would codify many of them. REGROW would force the FDA to conditionally approve stem cell therapies that frankly are just not ready for primetime, putting patients at great risk. Note that the big changes being lobbied for in FDA regulations would only apply to adult stem cells. I favor more careful changes at the FDA such as using Breakthrough designation for stem cells, something the FDA has not yet done. They should.

The fact that REGROW is floating out there also raises the stakes on CIRM’s lobbying as well. While CIRM officially takes no position on REGROW, their leader’s words and even those on the CIRM blog when talking about the huge changes they want at the FDA fit nicely with REGROW priorities.

It would be wonderful if we could start developing stem cell therapies, do early phase clinical trials, and then just give the experimental treatments right away to patients with a compelling expectation of safety and efficacy, but that is more a hopeful dream than a data-based reality. History would argue that rushing stem cell therapies to patients would be incredibly risky to them and likely do much harm. It’s just not that simple to say “step on the gas” without more data than early studies provide and without considering risks. Not only would many patients almost certainly be harmed, but also there would be big risks to the stem cell field overall too from the likely bad press of patients being harmed. The fact that BPC wants to charge patients for this would probably just add a financial insult to injury for some patients.

If you read Mills’ Fox News article and listen to his speech, there is no mention of risks of what he is proposing. He, BPC, and those favoring REGROW never mention the very real and common scientific and medical challenges to stem cell therapies. Without context, from their words you might assume that there are loads of stem cell therapies waiting in the wings that would absolutely be safe and effective for patients if only the big bad FDA system would get out of the way, but that’s just not reality. We should resist the temptation to turn the current FDA regulatory system into a political punching bag.

Another level of context here is that the dubious stem cell clinic industry is pushing against the FDA too. While CIRM has always opposed the clinics and I’m 100% sure it still does, I’m concerned that CIRM’s lobbying against the FDA could by accident help the clinics.

Prior to the Chronicle piece, I talked with Mills on the phone about the key issues that were on my mind. I greatly appreciate him taking the time to talk and I found it valuable, but it just reinforced my impression that the agency is committed to lobbying for weaker stem cell oversight. They truly believe this is the right thing to do. When I asked Mills about the aspirational language such as “miracles” in his Fox News piece, I got the sense that he feels passionately about the potential of adult stem cell therapies. There are a lot of strong feelings about stem cells, but plans should be built on a foundation of data.

Together all of this went into my decision to publicly raise concerns about the now more politically active CIRM in its new incarnation “CIRM 2.0” that is lobbying so hard against the FDA phased clinical trial system. Most of the stem cell scientists that I have talked to (admittedly with a few notable exceptions that include some long time stem cell advocates and scholars) are opposed to CIRM’s lobbying on this front, but are uncomfortable speaking out.

Today the question of what constitutes appropriate regulatory oversight is the biggest debate in the stem cell arena. It needs more discussion and debate out in the open.

Note that David Jensen’s California Stem Cell Report on Friday published an anonymous piece that was highly critical of the new CIRM for being too corporate. I didn’t write that piece as I always sign my name to what I write. Importantly, also I was unaware of that piece until after mine was published the day before.

3 Comments

First off you are correct to challenge CIRM …..The bottom line is getting produce out, Paul.

…….I would argue that CIRM funds the University system to early and with way to much money …….CIRM was and is like the little NIH funding system Old turks , young Turks networks …..These are things that the universities and federal government should fund ……Here is the problem Paul …… you need a system like the DARPA funding system with time lines and short term timelines …… . NO building and labs but collaborations on PI ‘s weak points ….. higher risk with higher rewards……treatments that was what the money was for …..Randy Mills is in a tough position and behind the eight ball ……Look at Jim Allison and CTLA-4 pathway treatment with blocking MABs…..or the sale of OCATA ( #1 stem cell company ,IMO ) to Astellas…….

If you want to effect signal pathways ones needs to understand the big picture of cellular functions and pre-eMSC blastomere stem cells and antigen processing and presentation are processes that occur within a cell that result in fragmentation of proteins, association of the fragments with major histocompatibility complex( MHC) I molecules, and expression of the peptide-MHC molecules at the cell surface where they can be recognized by the T cell receptor on a T cell. The path leading to the association of protein fragments with MHC molecules differs for class I CD8 T cells and TILS, CTLA-4 type cells and class II CD4 T cells MHC. MHC class I molecules present degradation products derived from intracellular (endogenous) proteins in the cytosol. MHC class II molecules present fragments derived from extracellular (exogenous) proteins that are located in an intracellular compartment.

What is a T cells? A T cell is a type of lymphocyte or white blood cell which is involved in the function of the immune system. These cells originate in the bone marrow, working their way into a gland called the thymus, where they mature: the “T” in “T cell” comes from “thymus.” In the thymus, the cells differentiate into different types of (Cluster Differentiation) CD3 T cells such as CD4 helper cells, TH1 andTH2 and TH17 CD16+56 natural killer cells, T regulatory cells, and CD8 cytotoxic cells.

Let’s say you have 2-5 million eMSC for treatment of say, MS. What happen to Immune system? The principal antigen presenting cells (APC) such as eMSC, macrophages, dendritic cells (Langerhans cells), and B cells, and the expression of class II MHC molecules is either constitutive or inducible, especially by cytokines and chemokines in the case of eMSCs.

Think of the eMSC as the framing of the house and the Immune system and other cells fills in the insulation, plumbing, electric wiring, sheath rock, painting of walls etc. So, the Reboot is replacing old cells in the infrastructure with new cells. It is like remodeling an old house that was built 100 years ago but has all the modern technology of today. You should have your memory T cells so you should not lose recall to foreign antigens, IMO.

CIRM is under public pressure to deliver clinical success. Under Proposition 71, expectations of Californians were raised by the promise of new therapies for numerous diseases – this expectation is now turning to frustration.

Mills has been tempering these expectations by stating that CIRM carries out work that pharmaceutical companies won’t because the return on investment is not yet attractive. That’s fair enough, but CIRM still has to get something through clinical trials to regain public support, and what better than to remove Phase III?

Only problem is, this rationale is not driven by the needs of patients, but by economics and politics, and actually increases risks for patients – a clear contradiction of CIRM’s primary mission.